Project Summary Funds are requested to apply technologies being developed in a current NIGMS award to gener- ate recombinant antibody-like a?nity reagents to the spike protein of the SARS-CoV-2 virus. As a proof-of-principle experiment, we have already isolated four ?bronectin type III (FN3) monobodies that bind with low nanomolar a?nity to the receptor binding domain (RBD) of the viral spike pro- tein. An administrative supplement will permit continuation and expansion of this work to generate a?nity reagents that bind with picomolar a?nity and can be used in sensitive, robust diagnostic assays (homogenous assays, lateral ?ow assays) for virus particles in saliva. Separately, these monobodies will be reformatted as bivalent Fc fusions and overexpressed in CHO cells. Such reagents have the potential to serve as therapeutic agents that lower or block viral entry into pa- tients ACE2-expressing cells. 1